Progression to end-stage renal failure is the final common pathway of various proteinuric nephropathies. The degree of proteinuria is associated with the rate of progression of renal disease.
In human proteinuric diseases, tubulointerstitial injury is a better predictor of renal function decline than is glomerular damage. Filtered tubulotoxic plasma proteins are believed to be responsible for this association, although the nature of these proteins is uncertain. Filtered proteins partly exert their detrimental effects via activation of proximal tubular cells (PTC), which excrete chemokines and cytokines, resulting in inflammation, myotransformation of interstitial fibroblasts, fibrosis, and apoptosis. This ultimately leads to end-stage renal failure. Renal tubular epithelial cells are therefore considered to be crucial in the progression of interstitial damage. Proteinuria has been proposed to cause tubular injury and interstitial fibrosis.
There is a continuing need in the art for determining and monitoring the kidney and liver function in animals and man after drug treatment or when kidney function is impaired due to a disease.